Diallyl sulfides: Selective inhibitors of family X DNA polymerases from garlic (Allium sativum L.) |
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Authors: | Masayuki Nishida Takahiko Hada Kouji Kuramochi Hideki Yoshida Yuko Yonezawa Isoko Kuriyama Fumio Sugawara Hiromi Yoshida Yoshiyuki Mizushina |
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Affiliation: | 1. Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan;2. Research and Development Department, Bizen Chemical Co., Ltd., Akaiwa-shi, Okayama 709-0716, Japan;3. Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan;4. Cooperative Research Center of Life Sciences, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan |
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Abstract: | Diallyl sulfides, organosulfur compounds isolated from garlic (Allium sativum L.), selectively inhibit the activities of mammalian family X DNA polymerases (pols), such as pol β, pol λ and terminal deoxynucleotidyl transferase (TdT), in vitro. The purified fraction (i.e., Sample-A) consisted of diallyl trisulfide, diallyl tetrasulfide and diallyl pentasulfide (molecular ratio: 5.3:3:1). Commercially purchased diallyl sulfides also inhibited the activities of family X pols, and the order of their effect was as follows: Sample-A > diallyl trisulfide > diallyl disulfide > diallyl monosulfide, suggesting that the number of sulfur atoms in the compounds might play an important structural role in enzyme inhibition. The suppression of human cancer cell (promyelocytic leukaemia cell line, HL-60) growth had the same tendency as the inhibition of pol X family among the compounds. Diallyl sulfides were suggested to bind to the pol β-like region of family X pols. |
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Keywords: | pol DNA-directed DNA polymerase (E C 2 7 7 7) TdT terminal deoxynucleotidyl transferase (E C 2 7 7 31) dsDNA double-stranded DNA BRCT BRCA1 C-terminus NLS nuclear localization signal HhH helix-hairpin-helix dTTP 2&prime -deoxythymidine 5&prime -triphosphate dNTP 2&prime -deoxyribonucleoside 5&prime -triphosphate DMSO dimethyl sulfoxide IC50 50% inhibitory concentration LD50 50% lethal dose NP-40 Nonidet P-40 |
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